Comprehensive Variant Effect Map of Parkin-Mediated Mitophagy in Parkinson's Disease

ABSTRACT: The development of Parkinson's disease has a substantial genetic basis. Variants in the PRKN gene account for roughly half of autosomal-recessive Parkinson's disease cases, yet most remain classified as variants of uncertain significance. PRKN encodes the E3 ubiquitin-protein ligase Parkin, which plays a key role in mitochondrial quality control by initiating mitophagy. In this work, we introduce a multiplexed mitophagy assay and measure the activity of more than 99% of all possible single amino acid substitution and nonsense variants of Parkin. The obtained activity landscape closely reflects known structural and functional aspects of Parkin, while also revealing new insights into specific functional effects across the protein. This dataset near-perfectly distinguishes pathogenic from ben

SUBMITTER: Erna, Sól Sigmarsdóttir 

PROVIDER: S-SCDT-10_1038-S44318-026-00959-X | biostudies-other |

REPOSITORIES: biostudies-other